Studies will be performed on cellular host defense mechanisms related to opportunistic infections. Investigation will concentrate on cryptococcosis as a model of such infections with special emphasis on killing of non-phagocytized organisms by lymphoid cells. The relative importance of this and other fungicidal mechanisms in vivo will be studied. In vitro assays of killing of cryptococci by separated phagocytic and non-phagocytic cells will be performed. There will be two main avenues of approach to determine the importance of factors influencing the outcome of infection: (1) use of an experimental model of infection in the guinea pig; (2) studies of purified subpopulations of leukocytes obtained from human peripheral blood. Use of an animal model will permit the study of those lymphoid cells which can kill cryptococci by a non-phagocytic mechanism. The development and localization of these cells as well as chemotactic responses during cryptococcal infection will be correlated with survival of animals. Transfer of protective immunity using lymphocytes and lymphocyte extracts will be attempted. Development of suppressor cells in infected animals will be examined. This will help to determine immunologic markers which correlate with fungicidal activity as well as the effect of immunosuppressive therapy and disease activity on fungicidal mechanisms in man.